The Orphan Drug Act of 1983 brought increased awareness to the need for new treatments for rare disease patients and provided incentives to pharmaceutical manufacturers of orphan treatments, including tax credits for the costs of clinical research, seven years of patent exclusivity, and the waiver of Prescription Drug User Fee Act (PDUFA) filing fees. Of the 3,500 drug designations issued by the Office of Orphan Products Development since 1983, more than 500 have resulted in marketing approval.1 Still, only 5 percent of the estimated 7,000 known rare diseases have a therapy approved by the U.S. Food and Drug Administration (FDA), leaving substantial unmet medical needs for patients.2
Challenges to clinical development and commercialization of orphan drugs are many. Although these challenges may be similar to non-orphan drug development and marketing, the solutions are often different in the context of a rare disease with which there is often little medical experience. The issues are also more acute with increasing rarity of the disorder. This paper is intended as a discussion of the commonly encountered hurdles in studying rare diseases and how a cohesive and holistic approach can mitigate issues and help bring new treatments to patients.